This application seeks support for the continuation and growth of a program of research directed toward better understanding of the molecular mechanisms and cellular functions of ion transport across cell membranes. Investigations of the molecular mechanism of ion transport seek to solve four major unsolved problems: First, the factors which determine the relative affinities of passive and active transport systems for anions as compared with cations (perm-selectivity) as well as for different ions of the same sign; second, the mechanisms which regulate the maximum rate of transport for each ion; third, the means by which scaler chemical bond energy is converted to vectorial work in the process of active transport; fourth, the ionic basis of the electrical properties of biological membranes. Researches on the cellular functions of ion transport include studies of the role of this process in the regulation of cell composition and volume, osmo-regulation, excitation, conduction, differentiation, and the de-differentiation characteristic of neoplasia. Experiments designed to answer questions relevant to these problems are carried out with model systems, particularly thin lipid bilayers, red cells, cardiac muscle and various marine plants and animals. The experiments involved observations under various conditions of the electrical properties, fluxes of tracer ions, immunological properties, ultrastructure as revealed by freeze-fracture electron microscopy, and chemico-physical properties as indicated by fluorescence, electron spin resonance, nuclear magnetic resonance and absorption spectroscopy of membranes.